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S C Fowler

Publications and source records attributed to S C Fowler.

At least 55 records · Page 3Linked to original sources
PubMed1991

Scopolamine attenuates the motor disruptions but not the attentional disturbances induced by haloperidol in a sustained attention task in the rat.

Rats were trained to perform a sustained attention task that required the subject to insert its head into a cylindrical "observation tunnel" and wait for the presentation of one of three spatially separated visual stimuli located on the upper portion of the tunnel circumference. Detection of a briefly (0.125 s) presented "correct" stimulus, followed by the rats' forward nose poke, resulted in access to a reinforcement dipper lifted through the orifice in the floor of the tunnel. Nose pokes to the two incorrect stimuli resulted in a 5-s time-out period. The task maximized attention and minimized movement requirements. Performance was characterized in terms of accuracy (i.e. errors of omission, and errors of commission), time on task, and latency to respond to the stimuli (i.e., reaction time). Haloperidol (0.04, 0.08, and 0.16 mg/kg) increased errors of omission and reaction time. However, lack of significant correlations between these two measures suggested that attentional accuracy may be independent of motor slowing produced by this neuroleptic. Scopolamine (0.2 mg/kg) alone increased both errors of omission and commission, but did not affect reaction time to correct stimuli. The sustained attention task as implemented here may be useful in the simultaneous study of classical neuroleptics desirable and undesirable CNS effects.

Animals↗
PubMed1991

Distinguishing between haloperidol's and decamethonium's disruptive effects on operant behavior in rats: use of measurements that complement response rate.

The behavioral effects of haloperidol (0.04 to 0.16 mg/kg) and nonparalytic doses of decamethonium (0.2 to 0.8 mg/kg) were studied with operant methods that permitted the measurement of response rate, peak force of response, duration of response, and duration of the rat's head entry into the reinforcement dipper well. Type of operant response topography (forelimb press or forelimb grasp-and-pull) and peak force (low or high) required for reinforcement delivery were independent variables. The low-force, press-topography condition yielded qualitatively different profiles for the two drugs. Haloperidol increased peak force and duration of operant response, increased maximum head entry duration, and temporally dissociated forelimb and head entry behavior. Decamethonium decreased force and duration of operant response, did not appreciably affect maximum head entry duration, and did not influence the normal temporal coupling of forelimb and head entry responses. The haloperidol effects were seen as reflections of pseudo-Parkinsonism, not muscle weakness, which appeared to be the primary source of decamethonium's behavioral effects.

Animals↗
PubMed1990

Haloperidol produces within-session increments in operant response duration in rats.

On the basis of previously reported observations that haloperidol induces within-session decrements in operant response rate in rats, it was suspected that other measures of operant behavior may also display within-session changes after treatment with this neuroleptic. Accordingly, haloperidol (0.02, 0.04, 0.08, 0.16 mg/kg) was administered to six rats trained on a fixed-ratio 20 schedule of liquid food reinforcement, and response duration was recorded as a measure of drug effects independent of response rate. Significant within-session decrements in response rate and increments in response duration were observed as responding ensued. At the 0.08 mg/kg dose, 300% increases in response duration were seen during the last third of the responses made in a session. The progressive slowing of individual motor acts were interpreted as neuroleptic-induced Parkinsonism in the rat, and within-session decrements in response rate were likewise seen as a manifestation of the same pharmacological effects that increased response duration.

Animals↗
PubMed1990

Effect of pCPA on nicotine-induced analgesia.

This study investigated the effect of para-chlorophenylalanine (pCPA), on nicotine-induced analgesia. pCPA reduces physiological levels of 5-HT, a neurotransmitter that has been linked to pain. The effects of naloxone HCl and mecamylamine HCl on this analgesia were also assessed. Subjects were 24 albino rats. Each group of eight rats was injected subcutaneously (SC) with nicotine sulphate, followed by an intraperitoneal (IP) injection of one of the potential antagonists. Behavioral analgesia was assessed using the tail-flick test. Data analysis revealed that pCPA did not affect nicotine-induced analgesia. Consistent with past research, naloxone also had no effect, and mecamylamine effectively eliminated this analgesia. The results are interpreted in light of current knowledge of this behavioral analgesia and pain perception, in general.

Analgesia↗
PubMed1990

A new rodent model for neuroleptic-induced pseudo-parkinsonism: low doses of haloperidol increase forelimb tremor in the rat.

Rats were trained to use the right forelimb to exert continuous downward pressure on a force transducer and simultaneously to drink sweetened milk from a dipper controlled by the emitted force. Oscillations in forelimb force during this performance were spectrally analyzed to describe the tremorogenic effects of haloperidol (0.04, 0.08, or 0.16 mg/kg). Haloperidol reduced time-on-task and increased the variance of force oscillations in the 10.0-25.0-Hz frequency band. When atropine sulfate (5 mg/kg) was given along with haloperidol, time-on-task was partially restored, and the effects of haloperidol on the 10.0-25.0-Hz band were diminished. These data suggest that the behavioral deficits produced by relatively low doses of haloperidol in rats are analogous (and possibly homologous) to neuroleptic-induced Parkinsonian symptoms in humans.

Animals↗
PubMed1989

Force-proportional reinforcement: pimozide does not reduce rats' emission of higher forces for sweeter rewards.

A two-step force-proportional reinforcement procedure was used to assess the efficacy of a sucrose reward under neuroleptic challenge. The force-proportional reinforcement method entails an increase in the quality of reward contingent upon higher force-emission. This paradigm was conceived as a rate-free means of addressing the putative anhedonic effects of dopaminergic receptor-blocking agents. Results failed to support the anhedonia interpretation of neuroleptic-induced response decrements: Pimozide did not diminish the ability of a high-concentration sucrose solution to maintain elevated response forces. Alternatives to the anhedonia interpretation were discussed with emphasis on the drug's motor effects in the temporal domain.

Animals↗
PubMed1988

Effects of pimozide, across doses and within sessions, on discriminated lever release performance in rats.

By using either water or food reinforcement, rats were trained to perform a discriminated lever release task (DLR), which required the rat to hold an operant lever in the closed position through one of five randomly presented foreperiods (2-6 s) and to release the lever within 0.5 s of the onset of a light discriminative stimulus. The procedure is analogous to the method used in human reaction time studies, except that here the procedure was free-operant, not fixed-trial. The effects of pimozide (0.12, 0.25, and 0.50 mg/kg) on this behavior were evaluated in terms of numbers of total responses, reinforced responses (successful releases), anticipatory responses, and extended responses (holding too long). Significant dose-dependent decreases in total responses and in reinforced responses were seen as supporting the hypothesis of a deficit in response initiation, which is often invoked to account for neuroleptic-induced reductions in discriminated active avoidance. Pimozide also increased the proportion of extended responses, suggesting that the drug affected the nature of responding as well as the tendency to respond. In the DLR task, pimozide produced substantial within-session decrements in both total responses and number of reinforced responses; however, extended responses exhibited within-session increases at the lowest dose. The results were discussed from both behavioral and pharmacological perspectives. The former emphasized motor effects and response initiation deficits, while the latter jointly considered neuronal responses to neuroleptic challenge and the dopamine release that results from behavioral activity itself.

Animals↗
PubMed1987

Some effects of pimozide on nondeprived rats' lever pressing maintained by a sucrose reward in an anhedonia paradigm.

The present work examined the generalizability of the anhedonia phenomenon (extinction-like responding with repeated neuroleptic treatment) by examining the effects of pimozide (PIM) on nondeprived rats lever pressing for a sucrose solution reward (32%) in an eight day dosing regime. The procedures used replicated the essential features of a previous study (Gramling et al. [10]) wherein the effects of PIM on rats licking directly a sucrose solution were assessed. Thirty nondeprived rats were trained to lever press on a CRF schedule for a 32% sucrose solution reward and then assigned to one of five treatment groups (N = 6). The treatment conditions included a no-reward group (EXT; vehicle injections), two pimozide (PIM) with reward conditions (either PIM 0.25 mg/kg + RWD or PIM 0.5 mg/kg + RWD), and a vehicle control group (RWD; vehicle injections). These four groups each received their respective injections and operant exposure for eight consecutive days. The fifth group was a home cage (HC) control condition wherein the rats were injected with 0.5 mg/kg PIM each test day but did not receive operant exposure until the fourth test day. The PIM treated rats exhibited a significant curvilinear pattern of responding on the rate measure across eight days of testing, whereas rats in the no-reward condition exhibited a significant downward linear trend across eight days of testing. Within-session analysis revealed that rats in the EXT group responded at significantly higher rates during the first five minutes of testing on the first test day compared to rats in the PIM 0.5 + RWD condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of pimozide on emitted force, duration and rate of operant response maintained at low and high levels of required force.

The behavioral effects of pimozide (0.25, 0.5, and 1.0 mg/kg) were assessed in two separate experiments in which session mean peak force, maximum peak force, and response duration served as the dependent variables complementing operant response rate. In the first experiment, two groups of water-deprived rats were trained on a continuous reinforcement (CRF) schedule for reaching out and pressing downward on a force transducer with peak forces of at least 4 g (low-force group) or 40 g (high-force group). In the second experiment a pull-type response topography and fixed ratio 20 were used, and force requirements were 4 g for the low-force group and 100 g for the high-force condition. Under these conditions pimozide decreased response rate and increased response duration irrespective of response topography, required force, or schedule of reinforcement. Neither mean peak force nor maximum peak force were significantly decreased by the drug, and in the low-force CRF condition a small but significant dose-related rise in mean peak force was observed. It was hypothesized that neuroleptics exert their motor-impairing effects primarily in the temporal domain of behavior but do not appreciably affect the force dimension of performance capacity. And these temporal domain effects may be reflected in differences in the kinetic requirements for the overall behavior and not just the response itself. Additionally, the possibility that some of the observed effects could be accounted for by "anhedonia" was addressed.

Animals↗
PubMed1986

Some effects of pimozide and of shifts in sucrose concentration on lick rate, duration, and interlick interval.

Multiple dependent measures were employed to characterize the licking behavior of rats exposed to shifts in reward magnitude or injected with pimozide (PIM). Nondeprived rats licked either a 32% (n = 14) or 4% (n = 15) sucrose solution in daily 10 min sessions. Rats in the 32% condition were then down-shifted to either a 16% (n = 7) 4% (n = 7) sucrose solution. Rats in the 4% condition were up-shifted to either 16% (n = 7) or 32% (n = 8) sucrose solution. The response profiles generated by those rats shifted to a lower reward magnitude were contrasted with either rats shifted from a 32% sucrose solution to a no-reward (plain tap water) condition, or with rats maintained on a 32% sucrose solution and administered the neuroleptic PIM (0.5 mg/kg or 1.0 mg/kg). Rats down-shifted from a 32% to 4% sucrose solution generated response profiles more similar to rats shifted to plain tap water than rats maintained on a 32% sucrose solution and administered PIM. These results suggested that PIM treatment is not functionally equivalent to either a shift to no-reward or to a shift to reduced reward conditions.

Animals↗
PubMed1986

Effects of haloperidol on the biophysical characteristics of operant responding: implications for motor and reinforcement processes.

Food-deprived rats were reinforced with sweetened condensed milk for pressing a force-sensing operandum on a continuous reinforcement basis. Force was continuously recorded (every 0.00195 sec) during each response, and measures derived from the resulting force-time waveforms served as the basis for evaluating neuroleptic challenge in the form of haloperidol (0.04, 0.08, 0.16 mg/kg). Significant dose-related drug effects included a decrease in response rate, an increase in mean emitted peak force, and an increase in overall response duration. Additional quantitative analyses revealed that the drug-induced increase in response duration resulted primarily from a slowing in the animal's paw removal from the force-sensing operandum. The findings are analogous to deficits in Parkinson's disease and suggest a behavioral mechanism that might account for much of the rate attenuating effects of neuroleptics. Implications for motor and reward interpretations of the actions of dopamine antagonists are also discussed.

Animals↗
PubMed1985

Effects of neuroleptics on rate and duration of operant versus reflexive licking in rats.

Operant conditioning techniques were used to train one group of nine rats to lick a dry horizontal metal disk on a fixed ratio 15 schedule with water reinforcement delivered at a different location. Another group of seven rats licked reflexively from a water reservoir positioned with the same spatial arrangements as the metal disk. The distance the rats' rongues traversed (10 mm) to contact the licking surface was the same in both the operant and reflexive lick conditions. The effects of three neuroleptics, haloperidol (0.06, 0.12, 0.24, 1.0, 2.0 mg/kg), chlorpromazine (0.5, 1.0, 2.0 mg/kg) and clozapine (2.5, 5.0, 7.5 mg/kg) on average lick rate and median lick duration were assessed for both groups. Dose related decreases in average lick rate were observed in both groups of rats as a function of dose of each of these neuroleptics. Moreover, operant lick rates were proportionately more affected by neuroleptic treatment than were reflexive lick rates. The dose-response effect for the duration variable was different for the two lick conditions in that reflexive lick duration was lengthened as dose increased, whereas operant lick duration was lengthened only at the lower doses of these drugs. The differential effect of these neuroleptics on operant vs. reflexive licking suggests that neuroleptics attenuate selectively those responses that require relatively more conditioning to acquire. These results may be analogous to the initiation deficit that has been suggested to account for neuroleptics' selective attenuation of avoidance, while leaving relatively intact the escape response in escape/avoidance procedures.

Animals↗
PubMed1984

Acute and subchronic effects of neuroleptics on quantitative measures of discriminative motor control in rats.

Operant-conditioning methods were used to train rats to reach through an opening in an operant chamber to exert forces on a silent, nearly isometric force-sensing manipulandum. The reinforcement contingency required the rat to hold forelimb force at 20-50 g for a minimum of 2 s. Once established, this 'hold-in-the-band' behavior yielded three measures of performance (time on task, number of reinforcers, variance of in-band force). Variance of in-band force was presumed to reflect steadiness of forelimb control. Acute drug effects on the three dependent variables were assessed for dose ranges of haloperidol (HAL), chlorpromazine (CPZ), clozapine (CLZ), and chlordiazepoxide (CDP). Moreover, the effects of HAL (0.5 mg/kg) and CLZ (5.0 mg/kg) were examined in a subchronic (28 day) dosing regimen. The acutely administered neuroleptics (HAL, CPZ, CLZ) produced dose-related decreases in time on task and number of reinforcers, but did not significantly affect variance of in-band force. The subchronic paradigm produced similar results. CDP did not significantly affect variance of in-band force and the 5.0 mg/kg dose produced a slight, but non-significant increase in time on task while significantly decreasing number of reinforcers; a trend opposite to that seen for the neuroleptics, which produced parallel effects on these two measures. The results suggest that the neuroleptics impaired performance by affecting the tendency to initiate responding instead of affecting the capacity to maintain steady forelimb force once a response was started.

Animals↗
PubMed1984

Some effects of pimozide on nondeprived rats licking sucrose solutions in an anhedonia paradigm.

The present work examines the generalizability of the anhedonia phenomenon (extinction-like responding with repeated neuroleptic treatment) by examining rats' licking behavior, a response heretofore untested, in the anhedonia paradigm. Nondeprived rats learned to lick a sucrose solution (32%) and were then tested for eight consecutive days in either a no-reward condition (N = 8) or two pimozide (PIM) with reward conditions (N = 8 at each of these two doses: 0.5 and 1.0 mg/kg). PIM treated animals did not exhibit rates or patterns of responding equivalent to animals in the extinction condition. Instead of an across session decline in rate, PIM treated animals showed a trend towards recovery on the rate measure. Within session patterns of responding of PIM treated animals more closely resembled animals in a normally rewarded condition responding at a generally lower rate, than animals in an extinction condition. The experimental procedure included the the use of home cage control animals, replication of the intermittent dosing procedure, and tests for transfer effects; all of these failed to produce patterns of responding typically obtained in the anhedonia paradigm when the response is lever pressing. Median lick duration and median interlick interval (ILI) were both lengthened with PIM treatment relative to injection control and extinction conditions, suggesting that pimozide treatment creates a motoric deficit. Taken together these results emphasize the importance of neuroleptics' motor vis a vis anhedonic effects.

Animals↗
PubMed1983

Chlordiazepoxide increases the force of two topographically distinct operant responses in rats.

By using operant conditioning techniques one group of 8 rats was trained to reach through a hole in the wall of an operant chamber, and to exert downward responses on a force-sensing circular disk. Eight other rats learned to reach through the hole and grasp and pull toward them a wire bail attached to a force transducer. Both behaviors were maintained on a fixed ratio 20 schedule of water reinforcement. The effects of chlordiazepoxide (CDP, 2.5, 5.0, 10.0 mg/kg) on response force and rate were assessed for both groups. CDP significantly increased response force in a dose-related manner in both groups; regardless of topography, response rate was little affected by the 2.5- and 5.0 mg/kg doses but was decreased by the highest dose. Results were discussed in terms of CDP's antipunishment and neuromuscular effects.

Animals↗